PD-L1 Expression in 65 Conjunctival Melanomas and Its Association with Clinical Outcome

Abstract

Conjunctival melanoma (CM) iss a rare and aggressive tumour that is increasing in frequency. The prognostic value of PD-L1 expression, alone or in combination with CD8 and PD-1 expression and the BRAF and NRAS status, has not been determined in CM to date. We evaluated the expression of PD-L1, CD8, PD-1 in CM and investigated whether there was an association between the expression of these markers and the BRAF and NRAS molecular profile as well as some clinico-pathological criteria. A total of sixty-five CM were assessed for PD-L1, PD-1, and CD8 expression by immunohistochemistry (IHC) and for BRAF and NRAS genomic alterations using molecular biology techniques and anti-BRAF and anti-NRAS antibodies. PD-L1 expression in tumour cells (TC) was very low or absent but detected in tumour-infiltrating immune cells (IC). A correlation was observed between the expression of PD-L1, CD8, and PD-1 in IC. No correlation between PD-L1 expression (in tumour and/or immune cells) and BRAF or NRAS mutations was observed. PD-L1 expression in IC correlated with a higher pTNM stage and PD-L1 expression in TC with worse disease-specific survival. PD-L1 expression is a potential prognostic biomarker that correlates with poor prognosis in CM patients.

Small but Challenging Conjunctival Melanoma: New Insights, Paradigms and Future Perspectives

“…Regarding innate and adaptive immune cells, no clear conclusion can be drawn because of the contradictory results regarding the role of tumour infiltrate lymphocytes (TILs) and tumour-associated macrophages (TAMs) [ 36 , 37 , 38 , 39 , 40 , 41 ]. Elevated levels of HLA Class I are associated with more TILs and TAMs and the expression of PD-L1 in CM seems almost similar to that found in cutaneous melanoma, even if lower percentages of expression levels have been reported [ 41 , 42 , 43 ]. The relevance of this predictive effect may be limited because, as with cutaneous melanoma, CMs with high PD-L1 levels have been shown to respond to PD-1 inhibitors [ 44 ].…”

“…Since then, numerous studies have been published supporting the fact that PD-1 inhibitors given alone were more effective than CTLA-4 inhibitors given alone, and that a combination of both immunotherapies could be more effective than monotherapy without increasing the adverse effects [ 111 ]. Several studies have reported an overexpression of PD-L1 in CM specimens, but it should be noted that immune cells within the TME showed a stronger staining than the tumour cells [ 12 , 43 ]. This could explain why the presence of peritumoral immune infiltrates has been associated with a better overall survival [ 12 ].…”

Need for a Dedicated Ophthalmic Malignancy Clinico-Biological Biobank: The Nice Ocular MAlignancy (NOMA) Biobank

“…As shown in Figure 8 , the number of publications related to ocular oncology published by our department has markedly increased over the last few years, both for fundamental and clinical research programs, mainly through the use of ocular resources from the biobank. Several articles based on the NOMA biobank resources have recently been published in peer-reviewed journals with high impact factors [ 1 , 6 , 49 , 50 , 51 ].…”

New Targeted Therapies and Immunotherapies for Locally Advanced Periocular Malignant Tumours: Towards a New ‘Eye-Sparing’ Paradigm?

“…Among cutaneous malignant tumours, melanoma has been the first tumour to show a clinical benefit due to immunotherapy progress. Several studies have shown that PD-L1 was expressed in cutaneous and conjunctival melanomas [ 41 , 42 ]. A pivotal study published in 2010 found, for the first time, an improved survival in patients with metastatic cutaneous melanoma treated with ipilimumab [ 43 ].…”